Article
Neurosciences
Ella Borgenheimer, Katherine Hamel, Carrie Sheeler, Francisco Labrada Moncada, Kaelin Sbrocco, Ying Zhang, Marija Cvetanovic
Summary: In the early stages of SCA1 in mice, there were no changes in the proportions of neurons and glial cells in the cerebellum, but Bergmann glia, velate astrocytes, and oligodendrocytes showed profound non-cell autonomous and potentially neuroprotective reactive gene and pathway alterations in response to Purkinje cell dysfunction.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Shelanah Salih, Zubair Ahmed Nizamudeen, Nigel De Melo, Lisa Chakrabarti, Virginie Sottile
Summary: Recent observations suggest that Bergmann glia in the cerebellum may play a role in tissue repair due to their expression of neural stem cell markers, although the physiological relevance of this overlap remains unclear in the absence of established in vivo evidence of tissue regeneration in the adult cerebellum.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Neurosciences
Vanessa L. Hull, Yan Wang, Travis Burns, Sarah Sternbach, Shuaishuai Gong, Jennifer McDonough, Fuzheng Guo, Laura N. Borodinsky, David Pleasure
Summary: Canavan disease is a pediatric leukodystrophy caused by mutations in the ASPA gene, resulting in a deficiency of the enzyme aspartoacylase. This leads to increased levels of N-acetyl-L-aspartate (NAA) in the brain and various neurological symptoms. In a mouse model of Canavan disease, researchers found that Bergmann glia (BG) exhibited significant morphological alterations and dysfunction, which preceded cerebellar degeneration. However, treatment with an antisense oligonucleotide targeting Nat8l, which reduces NAA production, was able to repair the BG and improve motor function. This suggests that restoring BG integrity may be a potential therapeutic strategy for Canavan disease.
Review
Cell Biology
Igor Y. Iskusnykh, Victor V. Chizhikov
Summary: Preterm birth and its associated factors have negative impacts on cerebellar development, which is involved in motor coordination, cognition, learning, memory, and social communication. Understanding the cellular and molecular mechanisms mediating cerebellar pathology affected by preterm birth is crucial for developing new treatment and neuroprotective strategies to improve cognitive, behavioral, and motor deficits in preterm individuals.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Neurosciences
Carmen Nanclares, Jose Antonio Noriega-Prieto, Francisco E. Labrada-Moncada, Marija Cvetanovic, Alfonso Araque, Paulo Kofuji
Summary: Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease characterized by progressive cerebellar ataxia. This study found that the intrinsic electrical properties of Purkinje cells (PCs) in SCA1 mice were altered, and these alterations were associated with the hyperexcitability of Bergmann glia (BG). Preventing BG hyperexcitability in SCA1 mice restored the normal function of PCs.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Neurosciences
Rui Zheng, Fang-Xiao Xu, Lin Zhou, Junyu Xu, Ying Shen, Ke Hao, Xin-Tai Wang, Junjie Deng
Summary: KIF2C is a protein that is believed to play a role in tumor progression, metastasis, neurodegenerative diseases, and psychiatric disorders. Our study shows that KIF2C is widely distributed in various regions of the brain and is localized in synaptic spines. It regulates microtubule dynamic properties, AMPA receptor transport, and cognitive behavior in mice.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Neurosciences
Vasiliki Tellios, Matthew J. E. Maksoud, Wei-Yang Lu
Summary: This study is the first to characterize BG morphology and GLAST expression during development in nNOS(-/-) mice using immunohistochemistry and western blotting. The results showed that BG in nNOS(-/-) mice exhibited abnormal morphology and decreased GLAST expression compared with wildtype (WT) mice across postnatal development. It was also found that nNOS/NO signaling regulates BG development through a PKG-mediated mechanism.
Article
Neurosciences
Takahiro Fujimoto, Kirsten Stam, Takeshi Yaoi, Kenta Nakano, Tetsuya Arai, Tadashi Okamura, Kyoko Itoh
Summary: This study aimed to investigate the expression profile of Dp71 in the cerebellum and found its presence in glial cells, Bergmann glial cells, and astrocytes, while Dp427 was exclusively expressed in inhibitory postsynapses within cerebellar Purkinje cells. Additionally, the study revealed biochemical associations of Dp71 with AQP4 and Kir4.1 in both the cerebellum and cerebrum, and partial co-localization of Dp71 with AQP4 and Kir4.1 in glial cells. The results suggest that different cell types in the cerebellum express different dystrophin molecular complexes, which may play a role in pathological and physiological processes through the regulation of water/ion channels and inhibitory postsynapses.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Neurosciences
Anton N. Shuvaev, Olga S. Belozor, Oleg Mozhei, Dariya A. Yakovleva, Ilya V. Potapenko, Andrey N. Shuvaev, Marina V. Smolnikova, Vladimir V. Salmin, Alla B. Salmina, Hirokazu Hirai, Anja G. Teschemacher, Sergey Kasparov
Summary: In cerebellar neurodegenerative diseases such as SCA1, reactive BG can negatively impact neuronal function and survival through compromised glutamate uptake. Excessive glutamate signaling appears to be a common feature in SCA1 pathology, contributing to cerebellar neurodegeneration.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
America Vera-Montecinos, Jordi Galiano-Landeira, Monica Roldan, Francisco Vidal-Domenech, Enrique Claro, Belen Ramos
Summary: METTL7A is mainly located in the endoplasmic reticulum and lipid droplets, with limited cellular expression in the brain. Reduced protein levels of METTL7A have been found in schizophrenia. Our study shows that METTL7A is highly expressed in Bergmann glia and has contacts with Purkinje neurons. The localization of METTL7A may play a role in maintaining cerebellar homeostasis and modulating cerebellar circuits.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Shahin Shabanipour, Xiaodan Jiao, Maryam Rahimi-Balaei, Mohamad Reza Aghanoori, Seung H. Chung, Saeid Ghavami, G. Giacomo Consalez, Hassan Marzban
Summary: This study investigates the role of NCAM1 in the development of Purkinje cells (PCs). The results suggest that NCAM1 expression is significantly upregulated when PCs fail to align and instead overmigrate into the molecular layer. This may indicate that NCAM1 plays a crucial role in the migration process of PCs.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Pharmacology & Pharmacy
Shu-Tao Xie, Wen-Chu Fan, Xian-Sen Zhao, Xiao-Yang Ma, Ze-Lin Li, Yan-Ran Zhao, Fa Yang, Ying Shi, Hui Rong, Zhi-San Cui, Jun-Yi Chen, Hong-Zhao Li, Chao Yan, Qipeng Zhang, Jian-Jun Wang, Xiao-Yang Zhang, Xiao-Ping Gu, Zheng-Liang Ma, Jing-Ning Zhu
Summary: Specific medications for cerebellar ataxias are still lacking, but the activation of cerebellar microglia has been found to be common in ataxic patients and rodent models. This study provides direct evidence that activating cerebellar microglia induces ataxia symptoms and worsens motor deficits in a mouse model of cerebellar ataxia. The activation of microglia leads to the hyperexcitation of Purkinje cells which triggers ataxia, and inhibiting microglia activation can alleviate motor deficits in mice.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Immunology
Chandrakanth Reddy Edamakanti, Vishwa Mohan, Puneet Opal
Summary: Using human SCA autopsy samples, researchers discovered inflammatory JNK-dependent c-Jun phosphorylation in Bergmann glia, and inhibiting the JNK pathway reduced Bergmann glia inflammation and improved the SCA1 phenotype both behaviorally and pathologically, suggesting a causal role for Bergmann glia inflammation in SCA1 and a potential therapeutic strategy.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Neurosciences
Satoshi Akinaga, Sayaka Harada, Miyuki Takahashi, Aosa Kaneko, Papachan Kolattukudy, Yoshio Goshima, Toshio Ohshima
Summary: The migration and alignment of cerebellar neurons are crucial for the development of the mammalian cerebellar cortex, and the genes CRMP1 and CRMP2 play important roles in this process. Loss of function of CRMP1 and CRMP2 leads to deficits in the migration and alignment of Purkinje cells in the cerebellar lobule X, and affects balance and grip power performance.
Article
Biochemistry & Molecular Biology
Anita Monteverdi, Danila Di Domenico, Egidio D'Angelo, Lisa Mapelli
Summary: In this study, the frequency dependence and spatial anisotropy of cerebellar activation were investigated using a high-throughput high-density multielectrode array. The results showed that mossy fiber inputs reached the Purkinje cell layer even at low frequencies, but the efficiency of transmission increased at higher frequencies. These findings provide important insights into the computational properties and pathological alterations of the cerebellar cortex.